The present results indicate that the addition of a fluorine moiety to the C-6 position of L-dopa and dopamine decreases their vulnerability to catabolism by catechol-O-methyl-transferase. This, in turn, drastically decreases the nonspecific background in positron emission tomography (PET) activity. The major metabolite of 6-F-dopa in the caudate nucleus is 6-F-dopamine, rather than O-methyl-6-F-dopa. The turnover rate of 6-fluorocatecholamine resembles that of 3H-catecholamine. This neurochemical evidence is the basis for the use of the presynaptic ligand fluorine-18 labeled 6-F-dopa in a PET procedure for imaging brain dopamine. By using the high resolution McMaster PET scanner, brain damage to striatal dopamine of MPTP-induced parkinsonian monkeys was visualized and quantified by using fluorine-18 labeled 6-F-dopa. The results indicate that the accumulation of fluorine-18 PET activity due to 6-F-dopamine is absent in a severe case of parkinsonism. This preclinical trial has demonstrated that the degree of brain damage in living parkinsonian monkeys appears to be quantifiable by this PET procedure. Thus, 6-F-dopa has fulfilled the criteria of an ideal presynaptic ligand for PET imaging of brain dopamine. This PET imaging procedure may prove to be a diagnostic tool for the detection and quantification of subclinical cases of Parkinson's disease after passing a preclinical toxicological evaluation. It has further been proposed to modify this PET procedure to measure the turnover rate of dopamine in the mesocortical and mesolimbic system and to evaluate the dopaminergic mechanism of clinical neuropyschiatric disorders.